This invention relates to certain esters and amides of suprofen having enhanced delivery characteristics on topical administration to the eye. This invention also relates to pharmaceutical compositions comprising such suprofen derivatives and to methods of using them when indicated to achieve an anti-inflammatory effect on topical delivery to the eye.
Suprofen, alpha-methyl-4-[2-thienylcarbonyl] benzeneacetic acid, is an inhibitor of prostaglandin biosynthesis with analgesic, antipurretic and anti-inflammatory properties. Suprofen was developed by Janssen Pharmaceutica; Beerse, Belgium, as disclosed in P. G. H. Van Daele, J. M. Boey, V. K. Sipido, M. F. L. De Bruyn, and P. A. J. Janssen; Arzneim-Forsch, (Drug Res.), 25 (10), 1495 (1975). This article is incorporated herein by reference to the extent that it teaches the preparation of suprofen and techniques of synthesis of certain esters and amides of suprofen which are described in that article, and which techniques, by analogy, provide an enabling disclosure on how to prepare the compounds of the present invention. The esters and amides of suprofen of the present invention are not disclosed by the incorporated by reference article and further the species disclosed in the prior art do not possess an attribute unique to the suprofen species of the present invention which property relates to their ability to be transported across the cornea and thus made available for the ophthalmic anti-inflammatory effect when administered to the eye. Beyond the disclosed original article relating to suprofen esters and amides, there appears to be no relevant prior art relating to suprofen derivatives and the ability of such suprofen species to be transported across the cornea for purposes of enhancing drug delivery. However, the use of suprofen per se and as complexed with certain xanthine derivatives for ophthalmic delivery for the purpose of achieving an anti-inflammatory effect is known. See for example, U.S. Pat. No. 4,559,343 which is directed to certain complexes of suprofen with xanthine derivatives for the indicated utility. This patent is incorporated herein by reference to the extent that its disclosure is relevant by analogy to an enabling disclosure of how to use suprofen, suprofen complexes, and suprofen derivatives and analogues in the treatment of ocular inflammation via topical delivery of pharmaceutical compositions comprising such suprofen entities.